{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T13:00:24Z","timestamp":1775048424950,"version":"3.50.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Clinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Measures of Complement Activation and inflammation in patientS with CoronAvirus DisEase 2019 (CASCADE) patients (<jats:italic>n<\/jats:italic> = 72), (clinicaltrials.gov: NCT04453527), classified as mild, moderate, or severe (by support needed to maintain SpO<jats:sub>2<\/jats:sub> &amp;gt; 93%), and healthy controls (HC, <jats:italic>n<\/jats:italic> = 20), were bioprofiled using 76 immunological biomarkers and compared using ANOVA. Spearman correlation analysis on biomarker pairs was visualised <jats:italic>via<\/jats:italic> heatmaps. Linear Discriminant Analysis (LDA) models were generated to identify patients likely to deteriorate. An X-Gradient-boost (XGB) model trained on CASCADE data to triage patients as mild, moderate, and severe was retrospectively employed to classify COROnavirus Nomacopan Emergency Treatment for covid 19 infected patients with early signs of respiratory distress (CORONET) patients (<jats:italic>n<\/jats:italic> = 7) treated with nomacopan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The LDA models distinctly discriminated between deteriorators, nondeteriorators, and HC, with IL-27, IP-10, MDC, ferritin, C5, and sC5b-9 among the key predictor variables during deterioration. C3a and C5 were elevated in all severity classes vs. HC (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). sC5b-9 was elevated in the \u201cmoderate\u201d and \u201csevere\u201d categories vs. HC (<jats:italic>p<\/jats:italic> &amp;lt; 0.001). Heatmap analysis shows a pairwise increase of negatively correlated pairs with IL-27. The XGB model indicated sC5b-9, IL-8, MCP1, and prothrombin F1 and F2 were key discriminators in nomacopan-treated patients (CORONET study).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Distinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1192765","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T11:27:12Z","timestamp":1693913232000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning"],"prefix":"10.3389","volume":"14","author":[{"given":"Laura","family":"Wiffen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon Gerard","family":"D\u2019Cruz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim W.","family":"Higenbottam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan A.","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Moellman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debajyoti","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clive","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wynne","family":"Weston-Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anoop J.","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2001017\/SUPPL_FILE\/NEJMOA2001017_DISCLOSURES.PDF","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"New Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"210138","DOI":"10.1183\/16000617.0138-2021","article-title":"COVID-19 pneumonia: pathophysiology and management","volume":"30","author":"Gattinoni","year":"2021","journal-title":"Eur Respir Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/JTH.14981","article-title":"COVID-19: a collision of complement, coagulation and inflammatory pathways","volume":"18","author":"Chauhan","year":"2020","journal-title":"J Thromb Haemostasis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.23750\/ABM.V91I4.10393","article-title":"Triage protocol for allocation of critical health resources during the COVID-19 health emergency","volume":"91","author":"Iacorossi","year":"2020","journal-title":"A review. 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